title: Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development.
abstract: The 22q13.3 deletion syndrome is characterized by a significant delay in language development, mental retardation, hypotonia, and autistic features. Cumulative evidence has shown that haploinsufficiency of the SHANK3 gene is a major cause of the neurological symptoms of the 22q13.3 deletion syndrome. Shank3, a multidomain protein containing the SH3 and PDZ domains, is thought to play an important role in the formation and function of synapses in the developing brain. In this study, we analyzed the SHANK3 gene in 128 autistic patients with manifestations similar to those seen in the 22q13.3 deletion syndrome. The results showed a 6-amino acid deletion upstream of the SH3 domain, a missense variant (arginine to histidine at amino acid position 656) in the PDZ domain, and the insertion or deletion of a repeated 10-bp GC sequence located 9-bp downstream from the 3' end of exon 11. None of these variants was found in 228 controls.
authors.affiliation: Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Waga
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ondo
authors.forename: Reiko
authors.initials: R
authors.lastname: Fukumura-Kato
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Uchino
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001321:Autistic Disorder / Q000150:complications* / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013064:Speech Disorders / Q000150:complications* / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human